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5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement
Article first published online: 27 JAN 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 6, pages 1545–1552, 15 March 2010
How to Cite
Widhalm, G., Wolfsberger, S., Minchev, G., Woehrer, A., Krssak, M., Czech, T., Prayer, D., Asenbaum, S., Hainfellner, J. A. and Knosp, E. (2010), 5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Cancer, 116: 1545–1552. doi: 10.1002/cncr.24903
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- Issue published online: 3 MAR 2010
- Article first published online: 27 JAN 2010
- Manuscript Accepted: 21 JUL 2009
- Manuscript Revised: 9 JUL 2009
- Manuscript Received: 5 MAY 2009
- diffusely infiltrating gliomas;
- nonsignificant contrast enhancement;
- 5-aminolevulinic acid;
- anaplastic foci;
- positron emission tomography;
- proliferation rate
Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.
5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum 11C-methionine positron emission tomography uptake (PETmax) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI).
Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PETmax in all patients. MIB-1 LI was significantly higher in 5-ALA–positive than in nonfluorescent areas within a given tumor.
The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments. Cancer 2010. © 2010 American Cancer Society.